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1.  Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline 
Neuropsychologia  2012;50(9):2165-2175.
The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer’s disease and mild cognitive impairment are evident in their performance on the semantic verbal fluency test. In addition to the semantic verbal fluency test score, several other performance characteristics sensitive to disease status and predictive of future cognitive decline have been defined in terms of words generated from semantically related categories (clustering) and shifting between categories (switching). However, the traditional assessment of clustering and switching has been performed manually in a qualitative fashion resulting in subjective scoring with limited reproducibility and scalability. Our approach uses word definitions and hierarchical relations between the words in WordNet®, a large electronic lexical database, to quantify the degree of semantic similarity and relatedness between words. We investigated the novel semantic fluency indices of mean cumulative similarity and relatedness between all pairs of words regardless of their order, and mean sequential similarity and relatedness between pairs of adjacent words in a sample of patients with clinically diagnosed probable (n=55) or possible (n=27) Alzheimer’s disease or mild cognitive impairment (n=31). The semantic fluency indices differed significantly between the diagnostic groups, and were strongly associated with neuropsychological tests of executive function, as well as the rate of global cognitive decline. Our results suggest that word meanings and relations between words shared across individuals and computationally modeled via WordNet and large text corpora provide the necessary context to account for the variability in language-based behavior and relate it to cognitive dysfunction observed in mild cognitive impairment and Alzheimer’s disease.
doi:10.1016/j.neuropsychologia.2012.05.016
PMCID: PMC3404821  PMID: 22659109
semantic verbal fluency; Alzheimer’s disease; mild cognitive impairment; semantic similarity; semantic relatedness; computational semantics
2.  Ecology of aging human brain 
Archives of neurology  2011;68(8):1049-1056.
OBJECTIVE
Alzheimer’s disease (AD), cerebral vascular brain injury (VBI), and isocortical Lewy body (LB) disease (LBD) are the major contributors to dementia in community- or population-based studies: Adult Changes in Thought (ACT) study, Honolulu-Asia Aging Study (HAAS), Nun Study (NS), and Oregon Brain Aging Study (OBAS). However, the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults is less clear.
DESIGN and SETTING
We evaluated 1672 brain autopsies from ACT, HAAS, NS, and OBAS of which 424 met criteria for CN.
MAIN OUTCOME MEASURES
Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque (NP) density, Braak stage for neurofibrillary tangles (NFTs), Lewy body (LB) distribution, and number of cerebral microinfarcts (CMIs).
RESULTS
47% of CN cases had moderate or frequent NP density; of these 6% also had Braak stage V or VI for NFTs. 15% of CN cases had medullary LBD; 8% also had nigral and 4% isocortical LBD. The presence of any CMIs was identified in 33% and high level CMIs in 10% of CN individuals. Overall burden of lesions in each individual and their co-morbidity varied widely within each study but were similar among studies.
CONCLUSIONS
These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker or neuroimaging studies as well as clinical trials that focus on community- or population-based cohorts.
doi:10.1001/archneurol.2011.157
PMCID: PMC3218566  PMID: 21825242
Alzheimer’s disease; vascular brain injury; Lewy body disease; cognitive aging

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